Safety and efficacy of nivolumab therapy in patients with metastatic renal cell carcinoma and impaired kidney function.

INTRODUCTION: Patients with renal insufficiency, usually defined as those with creatinine clearance < 40 mL/min, were excluded from pivotal clinical trials, especially in studies involving nivolumab therapy in patients with renal cell carcinoma (RCC). The aim of the study is to evaluate the efficacy and safety of nivolumab in patients with metastatic RCC (mRCC) stratified according to creatinine clearance. MATERIAL AND METHODS: Data from mRCC patients treated with nivolumab were retrospectively analyzed. Patients were classified into two categories according to their estimated glomerular filtration rate (eGFR); the first category (C1) included patients with eGFR < 40 mL/min/1.73 m2 and the second category (C2) included those with eGFR ≥ 40 mL/min/1.73 m2. RESULTS: Of the 95 patients enrolled, 1. group included 26 patients (27.4%) and 2. group included 69 patients (72.6%). None of the pts in category 1 were on hemodialysis. Overall incidence of adverse events was not statistically different between the two groups (P = .469). The overall response rate ORR was 50% in the first group and 42.0% in the second group (P = .486). Median overall survival (OS) was longer with 23.3 months in the 2. group versus 11 months in the 1. group (P = .415). CONCLUSION: Renal insufficiency is a common problem in patients with advanced renal cancer since they often undergo nephrectomy and their renal function may also worsen while receiving tyrosine kinase inhibitor therapy. We found that there is no significant difference in the safety and efficacy of nivolumab treatment between two groups. Nivolumab appears to be a safe and effective agent in patients with renal impairment.

The Impact of the D727E Polymorphism has no Significant Role in Multi Nodular Goiter.

Interactions between individual genetic and environmental factors determine the onset of the multi nodular goiter (MNG). The thyroid-stimulating hormone receptor (TSHR) gene is a convincing candidate gene in the pathogenesis of certain thyroid diseases including MNG. We investigated the codon 727 polymorphism (p.Asp727Glu, p.D727E) of the human TSHR gene using the polymerase chain reaction-restriction fragment length polymorphim (PCR-RFLP) methods in 31 Turkish patients with MNG and in 30 control subjects, aiming to evaluate the relationship between this polymorphism and MNG. After genomic DNA isolation, PCR amplification was performed using a pair of primers in exon 10 of the TSHR gene that contains the p.D727E polymorphism and digested by theNlaIII (Hin1II) restriction enzyme. We found the CC and CG genotype incidence for the patient group to be 0.71 and 0.29, respectively, and for the control group to be 0.8 and 0.2, respectively. No statistically significant difference was found between the genotype and allele distribution of both groups (p = 0.417 and p = 0.449, respectively). However, the polymorphism is significantly correlated with the low serum level of the TSH (p = 0.047). These results suggest that the p.D727E polymorphism of the TSHR gene may not contribute to the pathogenesis of nontoxic MNG diseases.

Heterotopic gastric mucosa in gallbladder associated with kidney agenesis and congenital hip dysplasia.

Heterotopic gastric tissue in the gallbladder is an extremely rare condition. There is not any specific clinical or laboratory finding and correct diagnosis is not possible before histopathological examination. Preoperative diagnosis usually resembles a polypoid Lesion or a fixed gallstone. We reported a 34-year-old female patient with heterotopic gastric mucosa in the gallbladder associated with congenital hip dysplasia and kidney agenesis. Laparoscopic cholecystectomy was performed and histopathology of the resected specimen showed that the "polyp" consisted of heterotopic gastric mucosa with glands of body and fundic type. Some cases of heterotopia in the gallbladder come from metaplasia, and may be one of the causes of gall bladder cancer. We discussed the clinical and histologic features of heterotopic gastric tissues and reviewed reported cases in the literature.

Multinodular leiomyoma of the esophagus with internodular hydropic degeneration and bulbous serosal protrusions similar to cotyledonoid uterine leiomyoma.

Leiomyoma is the most common benign tumor of the esophagus, and usually occurs as a solitary mass. We report a case of esophageal leiomyoma which shows multinodular growth pattern with bulbous serosal protrusions. The patient was a 26-year-old woman who had an esophageal ulcerated mass near the gastroesophageal junction. Clinical findings were consistent with carcinoma of the gastric cardia. Based on the clinical diagnosis, total gastrectomy with distal esophagectomy was performed. Histologic appearance of the resected specimen was consistent with leiomyoma which had a multinodular growth pattern.

Effects of radiotherapy on different histopathological types of rectal carcinoma.

BACKGROUND: Down staging by pre-operative chemoradiotherapy is currently considered part of the standard therapeutic approach to rectal carcinoma. The aim of this study was to assess the response to chemoradiotherapy of different histopathological types of rectal carcinoma with emphasis on the mucinous variant. METHOD: Between 1997 and 2002, 71 patients who received pre-operative chemoradiotherapy followed by surgery for rectal carcinoma were enrolled in the study. Staging of the rectal carcinoma was performed according to transrectal ultrasound findings (TN score) prior to the chemoradiotherapy. The chemoradiotherapy was followed by radical resection with mesorectal excision. All surgical specimens were examined by a single pathologist (MB). Pathological TN staging was assessed and tumour regression was graded according to a standard method (TRG1, complete response - TRG5 no response). Tumours were classified as mucinous or nonmucinous according to pre- and post-operative biopsy and specimen histopathological types. TN score change and TRG differences between groups were assessed. RESULTS: Tumour regression was seen after chemoradiotherapy in 94.4% of the patients, while in 5.6% of the patients no response was found. The change in TN score and TRG were correlated. Higher TRG was associated with a smaller decrease in TN staging. TRG was significantly lower in the nonmucinous compared to the mucinous group and the decrease in TN grade was significantly larger in the nonmucinous group. CONCLUSION: Mucinous carcinoma was associated with a lower response to pre-operative chemo-radiotherapy in this group of rectal carcinoma patients. Further studies are needed to determine its prognostic value.

Anatomic extent of colitis and disease severity are not predictors of pouchitis after restorative proctocolectomy for mucosal ulcerative colitis.

BACKGROUND: Pouchitis is a common complication following restorative proctocolectomy with ileal pouch anal anastomosis (RPC-IPAA) for mucosal ulcerative colitis (MUC). The aim of this study was to determine if perioperative anatomic extent and severity of disease are predictors of pouchitis. METHODS: All consecutive patients who underwent RPC-IPAA for MUC between 1988 and 2002 were retrospectively studied. Pouchitis was classified as acute, recurrent or refractory. Colectomy specimen slides were histopathologically evaluated by a single blinded pathologist (MB), who assessed extent and severity of disease. RESULTS: Of 112 patients assessed, 70 (62.5%) had some form of pouchitis at a median follow-up of 38 months (range, 1-204 months). No association was found between the extent or severity of disease and subsequent development of acute or chronic pouchitis. A positive correlation was found between the histopathologic score and the occurrence of clinical pouchitis (p=0.014). The presence of colonic metaplasia in the pouch biopsy was significantly correlated with a histopathologic diagnosis of pouchitis (p<0.0001, r=-0.449). CONCLUSIONS: Following RPC for MUC, the extent and severity of disease do not predict the subsequent development of pouchitis.

The role of ultrasonographic measurements of the median nerve in the diagnosis of carpal tunnel syndrome.

AIM: The aim of study was to assess the usefulness of ultrasonographic measurements of the median nerve in the diagnosis of carpal tunnel syndrome. MATERIALS AND METHODS: Eighty-six patients with carpal tunnel syndrome confirmed by electromyography and 45 asymptomatic controls were included in the study and underwent high-resolution ultrasonography of the wrists. The cross-sectional area and flattening ratio at the level of the pisiform bone of the proximal carpal tunnel were measured. Data from the patient group and control group were compared to determine the statistical significance. The accuracy of the ultrasonographic diagnostic criteria for carpal tunnel syndrome was evaluated using receiver-operating characteristic (ROC) analysis. RESULTS: One hundred and forty-eight wrists of 86 patients with carpal tunnel syndrome and 76 wrists of 45 control patients were examined. All measurements showed significant differences between patients and controls. Increased cross-sectional area of the median nerve was the most predictive measurement of carpal tunnel syndrome. Using the ROC curve, a cut-off value of >10.5 mm2 at the level of pisiform bone provided a diagnostic sensitivity of 89% and specificity of 94.7% CONCLUSION: The ultrasonographic measurement of the median nerve cross-sectional area is a sensitive, specific and useful non-invasive method for the diagnosis of carpal tunnel syndrome.

Effect of recombinant human granulocyte/macrophage colony-stimulating factor on the healing of colonic anastomosis in rats.

The purpose of this study was to investigate the efficacy of recombinant human granulocyte/macrophage colony-stimulating factor (rHuGM-CSF) on the wound healing of colonic anastomosis in rats. In total, 40 male Wistar rats were taken into this study. The control group (n = 20) received subcutaneous saline injection. The experiment group (n = 20) received rHuGM-CSF at 100 microg/kg subcutaneously. Both groups underwent colonic anastomosis 2 days later. In each group, burst pressure and hydroxyproline levels were determined 3 and 7 days after anastomosis. White blood cell (WBC) and red blood cell (RBC) counts were determined in each group to evaluate the effect of rHuGM-CSF on hematologic parameters in rats. There was no significant difference between the two groups in regard to burst pressure and hydroxyproline levels (p > .05). As expected, WBC counts significantly increased in the experiment group on days 3 (p = .035) and 7 (p = .046) following surgery. In conclusion, rHuGM-CSF administration and increased WBC counts did not have any positive effect on the wound healing of colonic anastomosis.

Haemostasis in patients with Behçet's disease.

AIM: to determine whether Behçet's disease affects haemostatic function. SETTING: University Hospital, Turkey. PATIENTS: one hundred and twenty-seven consecutive patients with Behçet's disease, 34 of whom with a history of vascular involvement. METHODS: prothrombin fragment 1+2 tissue plasminogen activator, protein S and C, antithrombin, fibrinogen, von Willebrand factor, thrombomodulin and prothrombin time (PT) were measured in patient plasma. RESULTS: soluble thrombomodulin was significantly lower and von Willebrand factor (vWF) and tissue plasminogen activator (tPA) significantly higher in Behçet's patients. Patients with vascular involvement showed the highest levels of vWF and tPA. There was no activation of coagulation, not even in patients with an active disease at the time of sampling. CONCLUSION: there were indirect signs of endothelial activity or damage, particularly in patients with vascular involvement. Coagulation was not activated.

Comparison of coagulation parameters for healthy subjects and Behçet disease patients with and without vascular involvement.

Behçet disease (BD) is an inflammatory illness that may attack several systems. Vascular involvement with thrombosis is one of the basic characteristics of this disease. The etiology of thrombosis tendency in BD has not been understood well. In this study, the role of primary coagulation parameters in patients with BD who have thromboembolic events was evaluated. In addition, the relation between the clinical activity of the disease and these parameters was compared. A total of 96 patients with a diagnosis of BD were studied at Ankara University, Medical School, Department of General Surgery and Behçet Center. BD patients were separated into two groups with respect to vascular involvement. Group A contained 22 patients with vascular attacks, and group B contained 74 patients without vascular attacks. In addition, 25 healthy persons comprised the control group (group C). The coagulation parameters assessed included protein C, protein S, antithrombin III activity, fibrinogen level, prothrombin time (PT), and partial thromboplastin time (PTT). There were no differences among the three groups with respect to protein C, protein S, fibrinogen, PT, and PTT values (p > 0.05). The antithrombin III value was found to be high in BD patients compared to those in the control group (p = 0.011). There was no difference regarding the antithrombin III value between BD patients with or without vascular attacks (p = 0.954). There was no correlation between the activity of disease and coagulation parameters (p > 0.05), but a positive correlation was seen between the duration of illness and vascular involvement. Fifty percent of patients who had had BD more than 8 years had vascular involvement (p = 0.002). We could not determine a specific pathology in relation to coagulation parameters that could explain the etiology of thrombosis in patients with BD. The elevated antithrombin III levels in patients with BD (compared to controls) may be due to a compensatory defense mechanism against increased procoagulant activity. There was a correlation between the duration of illness and vascular involvement.

The adverse effects of octreotide on the healing of colonic anastomoses in rats.

Octreotide, a long-acting somatostatin analogue, is widely used in gastrointestinal hypersecretory states and also for endocrine tumors in an attempt to inhibit the paracrine hormones. Although it is well known that octreotide inhibits trophic and anabolic hormones, no research has been conducted on its adverse effects on wound healing. In the present study, groups of rats were given 20 mcg/kg/day octreotide and 100 mg/kg/day hydrocortisone, the latter being the negative control group, starting 5 days preoperatively. The colonic anastomoses were assessed for healing on postoperative days (PODs) 5 and 8 by determining the bursting pressure of the anastomoses, performing histopathological analysis, and measuring the hydroxyproline content of the anastomotic tissues. Octreotide was found to affect anastomotic healing negatively on both PODs 5 and 8, but the negative effect of hydrocortisone was significant only on POD 8. No significant difference was found between the adverse effects of the two agents on POD 8. These findings indicated that octreotide has an adverse effect on the healing of colonic anastomoses in rats.

Partial sacral resection and reconstruction with bone cement. Discussion of an operative experience.

Sacral resection is often the only way for effective palliation of the severe pain in tumors involving sacrum. However the operation hardly seems to be acceptable with the reported operative times, blood losses and complication rates. A case of retrorectal leiomyosarcoma invading sacrum, with severe pain resistant to combined irradiation and chemotherapy is reported. The tumor was removed with resection of the right two thirds of S2, S3 and S4, and the sacrum was reconstructed with bone cement. Complete relief of the pain was obtained with no postoperative complications. It is concluded that incomplete resection of the sacral vertebrae should be performed for sacral root pain palliation if other methods fail. Bone cement reconstruction seems to be a valuable alternative to muscle flaps in covering sacral defects.